Endothelial injury has long been implicated in the initiation of atherosclerosis, but recent studies show there is little or no In Vivo endothelial cell loss. Furthermore, after a deliberate injury to the vessel wall, a rapid regeneration of the endothelium appears to prevent arterial lesion formation. The specific aims of this project are to examine the arterial endothelium in situations where deliberate or spontaneous injury has occurred. In particular, it will investigate endothelial cell replication, cell death and integrity, and platelet interactions with blood vessels of hyperlipemic animals. The project will also investigate the role of endothelial cell regeneration after deliberate injury, determine the capacity of regeneration, and the relevance of actual denudation in the context of intimal lesion formation. These studies will be carried out in both normal and cholesterol-fed animals. The above studies are part of an ongoing theme to investigate how and when a breakdown in endothelial integrity will initiate or exacerbate arterial lesion formation.